Nuclear receptors are ligand-regulated transcription factors that control diverse physiological and developmental processes. The focus of my laboratory is to understand the mechanism of signal transduction and transcriptional regulation by nuclear hormone receptors, including LXR alpha in cardiovascular disease, the glucocorticoid receptor (GR) in immune and neuronal function, and the androgen receptor (AR) in prostate cancer. We use state-of-the-art genetic (mouse knock-outs and knock-ins and CRISPR-Cas9 gene editing), biochemical (RNA-/ ChIP-seq and high-throughput siRNA and small molecules screens) as well as proteomic strategies to identify macromolecular complexes important in nuclear receptor activity to elucidate the mechanism of LXR, AR and GR function in vivo. Characterizing factors that control nuclear receptor activity can lead to potential new therapeutic strategies for prostate cancer, atherosclerosis as well as stress related anxiety, and depression.